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Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers.

ABSTRACT: Changes in cerebral blood flow are an essential feature of Alzheimer's disease and have been linked to apolipoprotein E-genotype and cerebral amyloid-deposition. These factors could be interdependent or influence cerebral blood flow via different mechanisms. We examined apolipoprotein E-genotype, amyloid beta-deposition, and cerebral blood flow in amnestic mild cognitive impairment using pseudo-continuous arterial spin labeling MRI in 27 cognitively normal elderly and 16 amnestic mild cognitive impairment participants. Subjects underwent Pittsburgh Compound B (PiB) positron emission tomography and apolipoprotein E-genotyping. Global cerebral blood flow was lower in apolipoprotein E ɛ4-allele carriers (apolipoprotein E4+) than in apolipoprotein E4- across all subjects (including cognitively normal participants) and within the group of cognitively normal elderly. Global cerebral blood flow was lower in subjects with mild cognitive impairment compared with cognitively normal. Subjects with elevated cerebral amyloid-deposition (PiB+) showed a trend for lower global cerebral blood flow. Apolipoprotein E-status exerted the strongest effect on global cerebral blood flow. Regional analysis indicated that local cerebral blood flow reductions were more widespread for the contrasts apolipoprotein E4+ versus apolipoprotein E4- compared with the contrasts PiB+ versus PiB- or mild cognitive impairment versus cognitively normal. These findings suggest that apolipoprotein E-genotype exerts its impact on cerebral blood flow at least partly independently from amyloid beta-deposition, suggesting that apolipoprotein E also contributes to cerebral blood flow changes outside the context of Alzheimer's disease.

SUBMITTER: Michels L

PROVIDER: S-EPMC4794091 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundArterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns.ObjectiveTo compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns.Design/methodsWe conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas.ResultsA total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001).ConclusionThis study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures.

Project description:BACKGROUND:With the disappointing outcomes of clinical trials on patients with Alzheimer's disease or mild cognitive impairment (MCI), there is increasing attention to understanding cognitive decline in normal elderly individuals, with the goal of identifying subjects who are most susceptible to imminent cognitive impairment. PURPOSE/HYPOTHESIS:To evaluate the potential of cerebral blood flow (CBF) as a biomarker by investigating the relationship between CBF at baseline and cognition at follow-up. STUDY TYPE:Prospective longitudinal study with a 4-year time interval. POPULATION:309 healthy subjects aged 20-89 years old. FIELD STRENGTH/SEQUENCE:3T pseudo-continuous-arterial-spin-labeling MRI. ASSESSMENT:CBF at baseline and cognitive assessment at both baseline and follow-up. STATISTICAL TESTS:Linear regression analyses with age, systolic blood pressure, physical activity, and baseline cognition as covariates. RESULTS:Linear regression analyses revealed that whole-brain CBF at baseline was predictive of general fluid cognition at follow-up. This effect was observed in the older group (age ?54 years, ??=?0.221, P?=?0.004), but not in younger or entire sample (??=?0.018, P?=?0.867 and ??=?0.089, P?=?0.098, respectively). Among major brain lobes, frontal CBF had the highest sensitivity in predicting future cognition, with a significant effect observed for fluid cognition (??=?0.244 P?=?0.001), episodic memory (??=?0.294, P?=?0.001), and reasoning (??=?0.186, P?=?0.027). These associations remained significant after accounting for baseline cognition. Voxelwise analysis revealed that medial frontal cortex and anterior cingulate cortex, part of the default mode network (DMN), are among the most important regions in predicting fluid cognition. DATA CONCLUSION:In a healthy aging cohort, CBF can predict general cognitive ability as well as specific domains of cognitive function. LEVEL OF EVIDENCE:1 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2018;48:449-458.

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Arterial spin labeling imaging reveals widespread and Aβ-independent reductions in cerebral blood flow in elderly apolipoprotein epsilon-4 carriers.

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